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    Clinical Trial Results:
    Phase 1-2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-PD-L1 Monoclonal Antibody BGB-A333 Alone and in Combination with Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients with Advanced Solid Tumors

    Summary
    EudraCT number
    		 2018-000265-37
    Trial protocol
    		 ES  
    Global end of trial date
    08 Sep 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    24 Nov 2021
    First version publication date
    19 Sep 2021
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Errors in time frame were corrected

    Trial information

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    Trial identification
    Sponsor protocol code
    BGB-900-101
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03379259
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    BeiGene, Ltd
    Sponsor organisation address
    BeiGene, Ltd., c/o BeiGene USA, Inc. 2955 Campus Drive, Suite 200 , San Mateo, California, United States, 94403
    Public contact
    BeiGene DDT Call Center, BeiGene Ltd., 1-877 828-5568, clinicaltrials@beigene.com
    Scientific contact
    BeiGene DDT Call Center, BeiGene Ltd., 1-877 828-5568, clinicaltrials@beigene.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Nov 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Sep 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1) For Phase 1: • To assess the safety and tolerability of BGB-A333 alone and in combination with tislelizumab in patients with advanced solid tumors • To determine the MTD, if any, and RP2D for BGB-A333 alone and in combination with tislelizumab 2) For Phase 2: To assess ORR per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 of BGB-A333 alone and in combination with tislelizumab in patients with selected tumor types
    Protection of trial subjects
    This trial was designed and monitored in accordance with Sponsor procedures, which comply with the ethical principles of GCP as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki. The IEC/IRB-approved ICF was signed and dated by the subject or the subject’s legally authorized representative before his or her participation in the study. A copy of each signed ICF was provided to the subject or the subject’s legally authorized representative. All signed and dated ICFs were retained in each patient’s study file or in the site file. For any updated or revised ICFs, written informed consent was obtained using the IEC/IRB-approved updated/revised ICFs for continued participation in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 28
    Country: Number of subjects enrolled
    New Zealand: 4
    Country: Number of subjects enrolled
    Spain: 7
    Worldwide total number of subjects
    39
    EEA total number of subjects
    7
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    16
    From 65 to 84 years
    23
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 8 study centers in Australia, 1 study center in New Zealand, and 3 study centers in Spain.

    Pre-assignment
    Screening details
    		 A total of 39 patients were enrolled in the study and all received ≥ 1 dose of study drug.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 1A: BGB-A333 450 mg
    Arm description
    		 BGB-A333 450 mg, intravenously, every 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGB-A333
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose ranging from 450 mg to 1800 mg, administered every three weeks

    Arm title
    		 Phase 1A: BGB-A333 900 mg
    Arm description
    		 BGB-A333 900 mg, intravenously, every 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGB-A333
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose ranging from 450 mg to 1800 mg, administered every three weeks

    Arm title
    		 Phase 1A: BGB-A333 1350 mg
    Arm description
    		 BGB-A333 1350 mg, intravenously, every 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGB-A333
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose ranging from 450 mg to 1800 mg, administered every three weeks

    Arm title
    		 Phase 1A: BGB-A333 1800 mg
    Arm description
    		 BGB-A333 1800 mg, intravenously, every 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGB-A333
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose ranging from 450 mg to 1800 mg, administered every three weeks

    Arm title
    		 Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Arm description
    		 BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGB-A333
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose ranging from 450 mg to 1800 mg, administered every three weeks

    Investigational medicinal product name
    BGB-A317
    Investigational medicinal product code
    Other name
    Tislelizumab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tislelizumab 200 mg, intravenously, every 3 weeks

    Arm title
    		 Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Arm description
    		 BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks (Urothelial Carcinoma Cohort)
    Arm type
    		 Experimental

    Investigational medicinal product name
    BGB-A333
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dose ranging from 450 mg to 1800 mg, administered every three weeks

    Investigational medicinal product name
    BGB-A317
    Investigational medicinal product code
    Other name
    Tislelizumab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tislelizumab 200 mg, intravenously, every 3 weeks

    Number of subjects in period 1
    		Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Started
    3
    3
    6
    3
    12
    12
    Completed
    2
    2
    3
    0
    3
    5
    Not completed
    1
    1
    3
    3
    9
    7
         Consent withdrawn by subject
    -
    -
    1
    -
    2
    -
         Disease progression
    -
    -
    -
    1
    -
    1
         Death
    -
    1
    2
    1
    4
    2
         Study terminated by sponsor
    -
    -
    -
    1
    -
    4
         Deteriorating condition
    -
    -
    -
    -
    1
    -
         Commenced new anti-cancer therapy
    1
    -
    -
    -
    -
    -
         Study terminated by sponsor
    -
    -
    -
    -
    1
    -
         Lost to follow-up
    -
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase 1A: BGB-A333 450 mg
    Reporting group description
    		 BGB-A333 450 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 900 mg
    Reporting group description
    		 BGB-A333 900 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 1350 mg
    Reporting group description
    		 BGB-A333 1350 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 1800 mg
    Reporting group description
    		 BGB-A333 1800 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Reporting group description
    		 BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Reporting group description
    		 BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks (Urothelial Carcinoma Cohort)

    Reporting group values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg Total
    Number of subjects
    		 3 3 6 3 12 12 39
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.0 ± 7.21 60.3 ± 11.24 58.8 ± 14.52 58.0 ± 16.52 65.3 ± 10.85 67.5 ± 8.52 -
    Gender categorical
    Units: Subjects
        Female
    		 2 2 4 2 7 1 18
        Male
    		 1 1 2 1 5 11 21
    PD-L1 Status
    Units: Subjects
        Positive
    		 0 2 2 1 4 6 15
        Negative
    		 2 1 3 2 7 6 21
        Missing
    		 1 0 1 0 1 0 3

    End points

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    End points reporting groups
    Reporting group title
    Phase 1A: BGB-A333 450 mg
    Reporting group description
    		 BGB-A333 450 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 900 mg
    Reporting group description
    		 BGB-A333 900 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 1350 mg
    Reporting group description
    		 BGB-A333 1350 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 1800 mg
    Reporting group description
    		 BGB-A333 1800 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Reporting group description
    		 BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Reporting group description
    		 BGB-A333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks (Urothelial Carcinoma Cohort)

    Subject analysis set title
    Phase 1A: BGB-A333 Monotherapy Dose Escalation
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Dose escalation cohorts

    Primary: Phase 1 and Phase 2: Number of Subjects with Adverse Events and Serious Adverse Events

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    End point title
    		 Phase 1 and Phase 2: Number of Subjects with Adverse Events and Serious Adverse Events [1]
    End point description
    Adverse events were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events NCI-CTCAE Version 4.03 SAEs were monitored from the date of informed consent. All adverse events (AEs) and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
    End point type
    Primary
    End point timeframe
    Up to 33.5 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No summary statistics available for discrete values.
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    12
    Units: Subjects
        Any Treatment Emergent Adverse Event (TEAE)
    1
    2
    6
    3
    12
    12
        Serious TEAE
    0
    1
    3
    1
    5
    3
    No statistical analyses for this end point

    Primary: Phase 1 and Phase 2: Number of Subjects with Abnormalities During Physical Examinations- Ophthalmology Findings

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    End point title
    		 Phase 1 and Phase 2: Number of Subjects with Abnormalities During Physical Examinations- Ophthalmology Findings [2]
    End point description
    Complete physical examination including an evaluation of 1) head, eyes, ears, nose, throat, 2) cardiovascular, 3) dermatological, 4) musculoskeletal, 5) respiratory, 6) gastrointestinal, and 7) neurological systems was required to be performed at Screening. At subsequent visits (or as clinically indicated), limited, symptom-directed physical examinations were performed. Clinically significant Ophthalmology abnormalities were collected from case report forms. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
    End point type
    Primary
    End point timeframe
    Up to 33.5 months
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No summary statistics available for discrete values.
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    12
    Units: Subjects
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Phase 1 and Phase 2: Number of Subjects with Abnormal Electrocardiograms (ECG)

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    End point title
    		 Phase 1 and Phase 2: Number of Subjects with Abnormal Electrocardiograms (ECG) [3]
    End point description
    Central ECG data was used and the abnormality was determined by the evaluator (Investigating physician). Multiple tests such as QT, HR, PR, RR were used by the evaluator to determine abnormality. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
    End point type
    Primary
    End point timeframe
    Up to 33.5 months
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No summary statistics available for discrete values.
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    12
    Units: Subjects
    0
    1
    5
    2
    1
    9
    No statistical analyses for this end point

    Primary: Phase 1 and Phase 2: Number of Subjects with Abnormal Lab Assessment Results

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    End point title
    		 Phase 1 and Phase 2: Number of Subjects with Abnormal Lab Assessment Results [4]
    End point description
    Lab abnormality was based on ANRIND: if the measurement value > ULN (upper limit of normal), it was considered Abnormal. All AEs and SAEs, were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
    End point type
    Primary
    End point timeframe
    Up to 33.5 months
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No summary statistics available for discrete values
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    12
    Units: Subjects
    3
    3
    6
    3
    12
    12
    No statistical analyses for this end point

    Primary: Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1

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    End point title
    		 Phase 2B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 [5] [6]
    End point description
    The ORR is defined as the percentage of participants who had confirmed Complete Response (CR) or Partial response (PR) assessed by investigator using RECIST version 1.1
    End point type
    Primary
    End point timeframe
    Up to 33.5 months
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No summary statistics available for discrete values
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No summary statistics available for discrete values.
    End point values
    		 Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    12
    Units: Percentage of participants
        number (confidence interval 95%)
    41.7 (15.17 to 72.33)
    No statistical analyses for this end point

    Primary: Phase 1A: Recommended Phase 2 Dose (RP2D) for BGB-A333

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    End point title
    		 Phase 1A: Recommended Phase 2 Dose (RP2D) for BGB-A333 [7]
    End point description
    RP2D for BGB-A333 alone and in combination with tislelizumab was the maximum tolerated dose (MTD) or less, which was determined by testing increasing doses up to 1800 mg.
    End point type
    Primary
    End point timeframe
    Up to 28 months
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No summary statistics available for discrete values
    End point values
    		 Phase 1A: BGB-A333 Monotherapy Dose Escalation
    Number of subjects analysed
    15
    Units: Milligrams
    1350
    No statistical analyses for this end point

    Secondary: Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1

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    End point title
    		 Phase 1A and Phase 1B: Overall Response Rate (ORR) Determined by Investigators Based on RECIST Version 1.1 [8]
    End point description
    ORR is defined as the percentage of participants who had confirmed CR or PR assessed by investigator using RECIST version 1.1
    End point type
    Secondary
    End point timeframe
    Up to 33.5 months
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint.
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    Units: Percentage of participants
        number (confidence interval 95%)
    0.0 (0.00 to 70.76)
    33.3 (0.84 to 90.57)
    50.0 (11.81 to 88.19)
    33.3 (0.84 to 90.57)
    16.7 (2.09 to 48.41)
    No statistical analyses for this end point

    Secondary: Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1

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    End point title
    		 Phase 2B: Duration of Response (DOR) Determined by Investigators Based on RECIST Version 1.1 [9]
    End point description
    DOR was defined as the time from the first determination of an objective response per RECIST version 1.1, until the first documentation of progression or death, whichever occurs first. DOR was not evaluable in Phase 1A and Phase 1B. 9999 = Data not estimable due to insufficient number of participants with events
    End point type
    Secondary
    End point timeframe
    Up to 33.5 months
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No summary statistics available for discrete values.
    End point values
    		 Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    12
    Units: Months
        median (confidence interval 95%)
    9.6 (6.0 to 9999)
    No statistical analyses for this end point

    Secondary: Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1

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    End point title
    		 Phase 1 and Phase 2: Disease Control Rate (DCR) Determined by Investigators Based on RECIST Version 1.1
    End point description
    DCR is defined as the proportion of participants with best overall response of CR, PR and Stable Disease.
    End point type
    Secondary
    End point timeframe
    Up to 33.5 months
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    12
    Units: Percentage of subjects
        number (confidence interval 95%)
    33.3 (0.84 to 90.57)
    33.3 (0.84 to 90.57)
    66.7 (22.28 to 95.67)
    66.7 (9.43 to 99.16)
    58.3 (27.67 to 84.83)
    75.0 (42.81 to 94.51)
    No statistical analyses for this end point

    Secondary: Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1

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    End point title
    		 Phase 2B: Progression-free Survival (PFS) Determined by Investigators Based on RECIST Version 1.1 [10]
    End point description
    PFS was defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of disease progression assessed by investigator using RECIST v1.1 or death, whichever occurs first
    End point type
    Secondary
    End point timeframe
    Up to 33.5 months
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint
    End point values
    		 Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    12
    Units: Months
        median (confidence interval 95%)
    6.1 (1.9 to 11.0)
    No statistical analyses for this end point

    Secondary: Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333

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    End point title
    		 Phase 1: Maximum Plasma Concentration (Cmax) of BGB-A333 [11]
    End point description
    PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling. Actual observed time values for PK sampling, have an allowable time deviation (+/- 3 days) from the planned nominal time as pre-specified in the Visit Window section of the study protocol.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint.
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    Units: ug/mL
        arithmetic mean (standard deviation)
    167 ± 42.4
    351 ± 151
    466 ± 91.0
    594 ± 150
    450 ± 127
    No statistical analyses for this end point

    Secondary: Phase 1: Time to Cmax (Tmax) of BGB-A333

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    End point title
    		 Phase 1: Time to Cmax (Tmax) of BGB-A333 [12]
    End point description
    PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint.
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    Units: Day
        median (full range (min-max))
    0.05 (0.04 to 0.21)
    0.06 (0.05 to 0.06)
    0.05 (0.05 to 0.22)
    0.06 (0.06 to 0.21)
    0.21 (0.05 to 0.22)
    No statistical analyses for this end point

    Secondary: Phase 1: Trough Serum Concentration (Ctrough) of BGB-A333

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    End point title
    		 Phase 1: Trough Serum Concentration (Ctrough) of BGB-A333 [13]
    End point description
    PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    Units: ug/mL
        arithmetic mean (standard deviation)
    21.3 ± 5.69
    47.0 ± 26.7
    90.7 ± 24.2
    81.4 ± 23.9
    80.0 ± 22.0
    No statistical analyses for this end point

    Secondary: Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333

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    End point title
    		 Phase 1: Time to Last Observed Concentration (Tlast) of BGB-A333 [14]
    End point description
    PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    12
    Units: Day
        median (full range (min-max))
    22.0 (21.0 to 22.0)
    21.0 (14.1 to 21.0)
    21.0 (14.0 to 22.0)
    21.0 (21.0 to 24.0)
    21.0 (7.10 to 24.0)
    No statistical analyses for this end point

    Secondary: Phase 1: Area Under the Concentration-time Curve From 9 to 21 Days Post-dose (AUC0-21day) of BGB-A333

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    End point title
    		 Phase 1: Area Under the Concentration-time Curve From 9 to 21 Days Post-dose (AUC0-21day) of BGB-A333 [15]
    End point description
    PK parameters were derived only for Phase 1A and Phase 1B. Phase 2B PK parameters were not estimated due to limited sampling.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (Pre-dose, End of infusion, 6 hours), Day 2, Day 4, Day 8, Day 15 and Day 21
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Not all arms in the Baseline Period are applicable for this endpoint
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    2
    5
    3
    11
    Units: ug*day/mL
        arithmetic mean (standard deviation)
    1095 ± 141
    2913 ± 320
    3823 ± 566
    4141 ± 648
    3546 ± 814
    No statistical analyses for this end point

    Secondary: Phase 1A and Phase 2: Number of Subjects with Detectable Treatment-emergent Anti-BGB-A333 Antibodies

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    End point title
    		 Phase 1A and Phase 2: Number of Subjects with Detectable Treatment-emergent Anti-BGB-A333 Antibodies
    End point description
    Treatment-emergent anti drug antibodies (ADA) was the sum of both treatment-induced ADA and treatment-boosted ADA, synonymous with "ADA incidence"
    End point type
    Secondary
    End point timeframe
    Up to 33.5 months
    End point values
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Number of subjects analysed
    3
    3
    6
    3
    11
    12
    Units: Subjects
    1
    1
    1
    0
    0
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the date of consent until study termination (approximately 33.5 months)
    Adverse event reporting additional description
    All adverse events were reported until either 30 days after the last dose of study drug or until initiation of a new anticancer therapy, whichever occurred first.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Phase 1A: BGB-A333 450 mg
    Reporting group description
    		 BGB-333 450 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 900 mg
    Reporting group description
    		 BGB-333 900 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 1350 mg
    Reporting group description
    		 BGB-333 1350 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1A: BGB-A333 1800 mg
    Reporting group description
    		 BGB-333 1800 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Reporting group description
    		 BGB-333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks

    Reporting group title
    Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Reporting group description
    		 BGB-333 1350 mg, intravenously, + Tislelizumab 200 mg, intravenously, every 3 weeks (Urothelial Carcinoma Cohort)

    Serious adverse events
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    1 / 3 (33.33%)
    5 / 12 (41.67%)
    3 / 12 (25.00%)
         number of deaths (all causes)
    0
    1
    2
    1
    4
    2
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Spinal cord compression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Generalised oedema
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonia aspiration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypophysitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vestibular neuronitis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Phase 1A: BGB-A333 450 mg Phase 1A: BGB-A333 900 mg Phase 1A: BGB-A333 1350 mg Phase 1A: BGB-A333 1800 mg Phase 1B: BGB-A333 1350 mg + Tislelizumab 200 mg Phase 2B: BGB-A333 1350 mg + Tislelizumab 200 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 3 (66.67%)
    6 / 6 (100.00%)
    3 / 3 (100.00%)
    12 / 12 (100.00%)
    12 / 12 (100.00%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
    2 / 3 (66.67%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    0
    1
    1
    2
    3
    2
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    3 / 12 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    3
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    1
    1
    0
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Perineal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    3 / 12 (25.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    1
    3
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    1
    1
    2
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    1
    0
    0
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    2
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    3 / 12 (25.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    4
    2
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    4 / 12 (33.33%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    1
    1
    4
    4
    Nausea
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
    4 / 12 (33.33%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    4
    0
    4
    0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    3 / 6 (50.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    3
    0
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Rash maculo-papular
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    1
    9
    1
    Pruritus
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    2
    1
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    5
    0
    1
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    2 / 3 (66.67%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    0
    2
    1
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    2 / 12 (16.67%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    2
    1
    Pain in extremity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    5
    0
    1
    0
    3
    Arthralgia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    7
    0
    Muscle spasms
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    2 / 12 (16.67%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    2
    0
    Infections and infestations
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    2 / 6 (33.33%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    2
    0
    0
    2
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    0 / 12 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Oral candidiasis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    2
    1
    0
    1
    Metabolism and nutrition disorders
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    1
    Hypercalcaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    1 / 3 (33.33%)
    1 / 12 (8.33%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    0
    1
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
    0 / 3 (0.00%)
    1 / 12 (8.33%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Jun 2018
    • BGB-A317 was replaced with its generic name tislelizumab. • The study design was revised so that for Phase 2A and Phase 2B, approximately 20 patients with UC were to be enrolled. The sponsor may have considered other tumor types including but not limited to non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, gastric cancer, MSI-high cancer, etc. Eligibility criteria for these cohorts was to be defined in future protocol amendments based on emerging clinical data. Sample size for Phase 2A and Phase 2B was adjusted. • The safety follow-up period was modified to include telephone contacts at Day 60 and Day 90 to assess immune-mediated AEs and concomitant medications, regardless of whether or not the patient started a new anticancer therapy. • The survival follow-up period was removed. • A requirement of antiviral therapy in patients with active hepatitis B was added, as was viral load testing. • Restrictions of hepatotoxic drugs, alcohol, and addictive drugs in patients with hepatocellular carcinoma were added. • Eye examinations were added. • The inclusion and exclusion criteria were revised. Patients who had detectable hepatitis B virus DNA at screening were to have the viral load test performed every 4 cycles, at the end of treatment visit, and when clinically indicated. • Tumor and response evaluations were revised so that tumor response would be assessed by the investigators using RECIST v1.1, and additional information on new lesions was collected according to iRECIST. The sponsor was to derive tumor response using iRECIST as an exploratory assessment. Imaging of the brain at screening was required for all patients. • The documentation method for SAE reporting was modified. • Creatine kinase and creatine kinase-MB tests were added. • The American Society of Clinical Oncology guideline and regulatory feedback on other studies of tislelizumab was added. • Child-Pugh classification was added.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    08 Sep 2020
    The sponsor decided not to pursue BGB-A333 as a monotherapy beyond the completion of dose escalation in Phase 1A. As such, Phase 2A was not conducted. Phase 1B was opened for dose expansion and enrolled 12 patients. For Phase 2B, only 1 cohort was opened for dose expansion and a total of 12 patients were treated in the metastatic UC arm. The sponsor terminated the study after Protocol Amendment 1 since the primary objective of assessing objective response rate (ORR) had been achieved.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Phase 2A of the study was not initiated nor conducted since BGB-A333 as a monotherapy treatment beyond the completion of dose escalation in Phase 1A was not pursued.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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